The research team led by Prof. Hongbin Yang has recently published an article titled Dopamine Release and Negative Valence Gated by Inhibitory Neurons in the Laterodorsal Tegmental Nucleus in Neuron on July 26, 2023, Beijing time. This research uncovered separate GABAergic subpopulations in a single brainstem nucleus that relay unpleasant stimuli to the mesolimbic DA system through direct and indirect projections, which is critical for establishing a circuit-level understanding of how negative valence is encoded in the mammalian brain.

 GABAergic neurons in the laterodorsal tegmental nucleus (LDT^GABA) encode aversion by directly inhibiting mesolimbic dopamine (DA). Yet, the detailed cellular and circuit mechanisms by which these cells relay unpleasant stimuli to DA neurons and regulate behavioral output remain largely unclear. Here, this research shows that LDT^GABA neurons bidirectionally respond to rewarding and aversive stimuli in mice. Activation of LDT^GABA neurons promotes aversion and reduces DA release in the lateral nucleus accumbens. Furthermore, this research identified two molecularly distinct LDTGABA cell populations. Somatostatin-expressing (Sst+) LDTGABA neurons indirectly regulate the mesolimbic DA system by disinhibiting excitatory hypothalamic neurons. In contrast, Reelin-expressing LDT^GABA neurons directly inhibit downstream DA neurons.

 Prof. Hongbin Yang from Zhejiang University MOE Frontier Science Center for Brain Science & Brain-Machine Integration is the corresponding author. Yonglan Du, Siyao Zhou, Chenyan Ma and Hui Chen are co-first authors. Ana Du, Guochuang Deng, Yige Liu also made significant contributions. This research was strongly supported by Prof. Shumin Duan and Prof. Lammel. This work was supported by grants from the STI2030-Major Projects, National Natural Science Foundation of China, NSFC-Guangdong Joint Fund-U20A6005, Key R&D Program of Zhejiang province, Fund for Medical Science and Key R&D Program of Guangdong Province, and the Fundamental Research Funds for the Central Universities.

原文链接：https://www.cell.com/neuron/fulltext/S0896-6273(23)00480-4